Despite the high burden of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) among adult men, very little is known about its etiology, symptom exacerbation or treated natural history. While a wide range of hypotheses have been proposed, few have been investigated in any great detail or using rigorous epidemiologic designs/methods. Additionally, few studies have described the treated natural history of CP/CPPS. Aim 1. To determine risk factors for the development of CP/CPPS using a multi-site, incident case-control study design (200 incident cases, 400 controls). Risk factors investigated will include early- and later-in-life biologic, behavioral and other factors focused around four central themes: 1) nutrients, alcohol intake and smoking; 2) weight history, and occupational and recreational activities impacting the pelvic area; 3) sexual and other urogenital exposures; and 4) concomitant medical conditions (e.g., fibromyalgia), family history of disease, abuse and stress. In contrast to previous studies, we will enhance our ability to draw causal inferences by a) comparing incident cases of CP/CPPS to carefully-selected controls without CP/CPPS to reduce the possiblity of temporal and selection biases; b) clinically evaluating cases and controls to rule out non-CPPS conditions and reduce the impact of misclassified diagnoses; and c) performing epidemiologic/biostatistical investigations to explore the possiblity of alternative, non-causal explanations. Aim 2. To determine risk factors for CP/CPPS symptom exacerbation and describe the treated natural history of CP/CPPS using a multi-site prospective, longitudinal study of 400 mainly prevalent CP/CPPS patients. We will compare each patient's recent exposures at visits when he has exacerbated symptoms to the same patient's recent exposures at visits when he has few or no symptoms to avoid selection bias and greatly minimize differences between comparison visits. We will use this design to investigate the same four themes of risk factors as in aim 1 and to describe the treated natural history of CP/CPPS. To our knowledge, this study will be the one of the first epidemiologic studies of risk factors of CP/CPPS symptom exacerbation. Together, these studies address a critical barrier to progress in the field of CP/CPPS research by investigating current, important hypotheses using appropriate and sophisticated epidemiologic methods.